EGFR and head and neck squamous cell carcinoma: Currently, cetuximab is the only FDA approved targeted therapeutic for HNSCC,8 and was selected based on pervasive overexpression of EGFR and its associations with outcomes in HNSCC.9,10 As with other targeted therapies, virtually all HNSCC patients develop acquired resistance limiting its clinical application.11 The near universal emergence of resistance and intermediate time rate at which it occurs mark cetuximab treatment in HNSCC as an ideal model system to study resistance.